Use of phenylethylamine derivatives for the antimicrobial treatment of surfaces

ABSTRACT

The use of compounds of formula (1) is described, in which compounds R 1 , R 2  and R 3  are each independently of the others hydrogen; C 1 -C 20 alkyl; C 3 -C 7 cycloalkyl; C 2 -C 20 alkenyl; C 4 -C 7 cycloalkenyl; C 2 -C 20 alkynyl, C 4 -C 7 cycloalkynyl; or unsubstituted or C 1 -C 5 alkyl-, C 3 -C 7 cylcoalkyl-, C 1 -C 5 alkoxyl-, C 3 -C 7 cycloakoxy-, halo-, oxo-, carboxy-, carboxy-C 1 -C 7 alkyl ester-, carboxy-C 3 -C 7 cylcloalkyl ester-, cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- or di-C 1 -C 20 alkylamino- or nitro-substituted phenyl-C 1 -C 5 alkyl, naphthyl-C 1 -C 5 alkyl, phenylcarbonyl-C 1 -C 5 alkyl, naphthylcarbonyl-C 1 -C 5 alkyl, pyrrolylalkyl, furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl, oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl, 1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl, 1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl, 1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl, pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl, pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl, pyridazinyl, quinolinyl or isoquinolinyl; R 4 , R 5 , R 6  and R 7  are each independently of the others hydrogen; C 1 -C 20 alkyl; C 3 -C 7  cycloalky; C 2 -C 20 alkenyl; C 4 -C 7 cycloalkenyl; C 2 -C 20  alkynyl; or C 4 -C 7  cycloalkynyl; and m and n are each independently of the other 0 or 1, for antimicrobial treatment of surfaces. The compounds exhibit a pronounced activity against pathogenic gram-positive and gram-negative bacteria, and also against yeasts and moulds. They are accordingly suitable for the antimicrobial treatment, especially preservation and disinfection, of surfaces.

[0001] The present invention relates to the use of selectedphenylethylamine derivatives for the antimicrobial treatment ofsurfaces, as antimicrobial active substances against gram-positive andgram-negative bacteria, yeasts and fungi and also in the preservation ofcosmetics, household products, textiles and plastics and for use indisinfectants, and to the preparation of such compounds.

[0002] The phenylethylamine derivatives used according to the inventioncorrespond to formula

[0003] wherein

[0004] R₁, R₂ and R₃ are each independently of the others hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted or C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-, car-boxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pen-tafluoroethyl-, amino-, N,N-mono- orN,N-di-C₁-C₂₀alkylamino- or nitro-substituted phenyl, phenyl-C₁-C₅alkyl,biphenyl, biphenyl-C₁-C₅alkyl, naphthyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl;

[0005] R₄, R₅, R₆ and R₇ are each independently of the others hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; or C₄-C₁₂cycloalkynyl; and

[0006] m and n are each independently of the other 0 or 1.

[0007] C₁-C₂₀Alkyl denotes a straight-chain or branched alkyl radical,e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl,amyl, isoamyl or tert-amyl, heptyl, octyl, isooctyl, nonyl, decyl,undecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl,octadecyl or eicosyl.

[0008] C₃-C₁₂Cycloalkyl denotes, for example, cyclopropyl, cyclobutyl,cyclopentyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl,cycloundecyl, cyclodocecyl or especially cyclohexyl.

[0009] Alkenyl includes, within the scope of the meanings given, interalia allyl, isopropenyl, 2-butenyl, 3-butenyl, isobutenyl,n-penta-2,4-dienyl, 3-methyl-but-2-enyl, n-oct-2-enyl, n-dodec-2-enyl,isododecenyl, n-dodec-2-enyl and n-octadec-4-enyl.

[0010] C₁-C₅Alkoxy denotes a straight-chain or branched radical, e.g.methoxy, ethoxy, propoxy, butoxy or pentyloxy.

[0011] According to the invention, preference is given to the use ofcompounds of formula (I) wherein

[0012] R₄, R₅, R₆ and R₇ are hydrogen, and especially of compounds offormula (I) wherein

[0013] n is 0; and

[0014] m is 1.

[0015] Special preference is given to compounds of formula

[0016] wherein

[0017] R₂ and R₃ are each independently of the other phenyl-C₁-C₅alkylunsubstituted or substituted by C₁-C₅alkyl, C₂-C₆alkenyl,C₃-C₁₂cycloalkyl, C₁-C₅alkoxy, C₃-C₁₂cycloalkoxy, halogen, oxo, carboxy,carboxy-C₁-C₇alkyl ester, carboxy-C₃-C₁₂cycloalkyl ester, cyano,trifluoromethyl, pentafluoroethyl, amino, N,N-mono- orN,N-di-C₁-C₂₀alkylamino or by nitro.

[0018] According to the invention, special preference is given to theuse of compounds of formula (2) wherein

[0019] R₂ and R₃ are C₁-C₅alkyl or C₄-C₁₂cycloalkyl.

[0020] According to the invention, preference is given also to the useof compounds of formula (2) wherein R₂ and R₃ are C₂-C₆alkenyl.

[0021] According to the invention, preference is given also to the useof compounds of formula

[0022] wherein

[0023] R₁, R₂ and R₃ are each independently of the othersphenylcarbonyl-C₁-C₅alkyl unsubstituted or substituted by C₁-C₅alkyl,C₂-C₆alkenyl, C₄-C₁₂cycloalkyl, C₁-C₅alkoxy, C₃-C₁₂cycloalkoxy, halogen,oxo, carboxy, carboxy-C₁-C₇alkyl ester, carboxy-C₃-C₁₂cycloalkyl ester,cyano, trifluoromethyl, pentafluoroethyl, amino, N,N-mono- orN,N-di-C₁-C₂₀alkylamino or by nitro.

[0024] Special preference is given to compounds of formula (3) wherein

[0025] R₁, R₂ and R₃ are each independently of the others C₁-C₅alkyl orC₄-C₁₂cycloalkyl, and also to compounds of formula (3) wherein

[0026] R₁, R₂ and R₃ are each independently of the others C₂-C₆alkenyl.

[0027] The following Table 1 lists further examples of phenylethylaminederivatives used according to the invention: TABLE 1a General structuralformula

Com- pound Purity [%] of (HPLC formula R₁ = R₂ 214 nm)  4

96  5

95  6

95  7

95  8

85  9

99 10

99 11

99 12

99 13

99 14

99 15

97 16

99 17

82 18

94 19

91 20

94 21

91 22

98 23

92 24

99 25

99 26

90 27

99 28

99 29

92 30

98 31

88 32

99 33

99 34

84 35

88 36

89 37

94 38

86 39

85 40

82 41

97 42

86 43

94 44

98 45

95 46

90 47

80 48

87 49

79 50

82 51

90 52

86 53

98 54

92

[0028] TABLE 1b General structural formula

Com- pound of formula R₁ = R₂=R₃ Purity [%] 55

91 56

80 57

87 58

86 59

99 60

98 61

98 62

96 63

97 64

95 65

96 66

93 67

94 68

94 69

96 70

94 71

85 72

99 73

99 74

86 75

96 76

96 77

95 78

95 79

96 80

95 81

99 82

99 83

94 84

99 85

99 86

99 87

90 88

95 89

98 90

98 91

93 92

93 93

99 94

90 95

98 96

88 97

>99 98

93 99

>99 100  —O—CH₃ n-C₁₂H₂₅ 101  H n-C₁₂H₂₅ 102  —O—C₆H₁₃ n-C₆H₁₃

[0029] The phenylethylamine derivatives used according to the inventionare preferably prepared in solid-phase synthesis using a trityl resinaccording to the following scheme:

[0030] in which

[0031] R is C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl;C₄-C₁₂cycloalkenyl; C₃-C₂₀alkynyl; C₄-C₁₂-cycloalkynyl; or unsubstitutedor C₁-C₅alkyl-, C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-,halo-, oxo-, carboxy-, carboxy-C₁-C₇alkyl ester-,carboxy-C₃-C₁₂cycloalkyl ester-, cyano-, trifluoromethyl-,pentafluoroethyl-, amino-, N,N-mono- or N,N-di-C₁-C₂₀alkylamino- ornitro-substituted phenyl, phenyl-C₁-C₅alkyl, biphenyl,biphenyl-C₁-C₅alkyl, naphthyl-C₁-C₅alkyl, phenylcarbonyl-C₁-C₅alkyl,naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl, furanylalkyl,thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl, oxazolylalkyl,thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl;

[0032] X is F, Cl, Br, I or hydroxy; and

[0033] n is from 1 to 3.

[0034] For that process, 2-(mono-, di- or tri-hydroxyphenyl)ethylamines,such as dopamine or hydroxydopamine hydrochloride, are dissolved in asuitable solvent, for example dichloromethane, DMF, THF, DMA(N,N-dimethylacetamide) or toluene, and an auxiliary base, for exampleDIPEA (ethyldiisopropylamine) or triethylamine, is added thereto. Tothat mixture there are added dropwise, per OH group, from 1 to 2equivalents of a trialkylchlorosilane, for example TMSCl (trimethylsilylchloride), TIPS-Cl (triisopropylchlorosilane) or TBDMS-Cl(tert-butyldimethylchlorosilane). After stirring for from 1 to 2 hoursat a temperature of from 0° C. to 50° C., preferably at 25° C., tritylchloride-polystyrene resin (TCP) or 2-chlorotrityl chloride-polystyreneresin is added.

[0035] The resulting suspension is shaken for from S to 20 hours at atemperature of from 0 to 25° C. Unreacted resin is quenched by theaddition of methanol. The resin is then washed thoroughly with varioussolvents (e.g. DMF, methanol, dichloromethane, THF or diethyl ether).

[0036] In order to remove the trialkylsilyl groups, the resin is thenreacted with 2 equivalents of TBAF (tetrabutylammonium fluoride) in THFover a period of from 1 to 5 hours. The resin is suction-filtered offand washed as described above.

[0037] There are three different methods available for alkylating thepolymer-bound hydroxyphenylethylamines.

[0038] 1st method: the loaded resin is shaken with from 10 to 30equivalents of DIPEA and from 10 to 20 equivalents of a suitable alkylhalide for 16 hours in a suitable solvent, e.g. DMF or dichloromethane,at a temperature of from 0 to 50° C. In order to complete the reaction,the reaction step is repeated.

[0039] 2nd method: the loaded resin is swelled in a suitable solvent,e.g. DMF or dichloromethane, and from 10 to 20 equivalents of BEMP(2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorin)and from 10 to 20 equivalents of alkyl halide are added thereto. Themixture is shaken for from 10 to 24 hours at a temperature of from 25 to60° C.

[0040] 3rd method: the polymer-bound hydroxy groups can also bealkylated by means of a Mitsunobu reaction. For that purpose the resinis swelled in a suitable solvent, e.g. DMF, dichloromethane or THF, andfrom 2 to 10 equivalents of triphenylphosphine are added. From 2 to 10equivalents of DEAD, DIAD or azidodicarboxylic acid dipiperidide arethen added.

[0041] Finally from 2 to 12 equivalents of alcohol are added and shakingis carried out for 24 hours at from 0 to 50° C. The resin is washed anddried as described above.

[0042] In order to isolate the end products from the resin, an acid,e.g. trifluoroacetic acid in dichloromethane or a mixture of aceticacid/methanol/dichloromethane, is added to the resin and shaking iscarried out for from 1 to 6 hours at 25° C. Filtration is then carriedout, and the filtrate is concentrated to dryness in vacuo. The oilyresidue which remains behind is lyophilised from tert-butylalcohol/water 4:1.

[0043] As an alternative to solid-phase synthesis, some phenylethylaminederivatives, which correspond to the formula

[0044] wherein

[0045] R is C₁-C₂₀alkyl; C₃-C₇cycloalkyl; or phenyl-C₁-C₅alkylunsubstituted or substituted by C₁-C₅alkyl, C₃-C₇cycloalkyl,C₁-C₅alkoxy, C₃-C₇cycloalkoxy, halogen, oxo, carboxy, carboxy-C₁-C₇alkylester, carboxy-C₃-C₇cycloalkyl ester, cyano, trifluoromethyl,pentafluoroethyl, amino, N,N-mono- or N,N-di-C₁-C₂₀alkylamino or bynitro; and

[0046] n is from 1 to 3;

[0047] can be prepared in liquid-phase synthesis by alkylation of ann-hydroxybenzoic acid alkyl ester (step 1), hydrogenation with LiAIH₄ toform an alkylated benzyl alcohol (step 2), reaction with thionylchloride to form the corresponding alkyl halide compound (step 3),reaction with KCN to form the corresponding nitrile compound (step 4)and then reduction with LiAIH₄ to form the amino compound of formula(103) (step 5), according to the following scheme:

[0048] The invention relates also to that process.

[0049] The phenylethylamines used according to the invention can also beprepared by alkylation of the deprotonated phenol or mono- ordi-hydroxyphenol, subsequent reaction with phosphorus oxychloride and anN,N-dialkylated amide and isolation of the benzaldehyde after hydrolysis(reaction step (1a)), or by reaction of the phenol or mono- ordi-hydroxyphenol with phosphorus oxychloride and an N,N-dialkylatedamide, alkylation (reaction step (1b)), heating of the aldehyde with amixture of ammonium acetate and a nitroalkane in a suitable solvent andcatalytic hydrogenation of the nitrostyrene to form the phenylethylamine(reaction step (2)), according to the following reaction scheme:

[0050] In that reaction scheme

[0051] R₁ and R₂ are each independently of the other hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀-alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted or C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-, carboxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- ordi-C₁-C₂₀alkylamino- or nitro-substituted phenyl, phenyl-C₁-C₅alkyl,biphenyl, biphenyl-C₁-C₅alkyl, naphthyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl;

[0052] X is Cl, Br or I; and

[0053] m is from 0 to 2.

[0054] For the reaction, according to reaction step (1a), phenol or amono- or di-hydroxyphenol are dissolved in a suitable solvent, e.g. DMF,toluene, xylene, dioxane, etc., and deprotonated with a suitable amountof a base, e.g. NaOH, Na₂CO₃, NaOMe, NaOEt, NaOtert-Bu, DIPEA,triethylamine, etc.. The appropriate chloride, bromide or iodide (R₁-X)is then added dropwise, with heating at from 40 to 120° C. When thereaction is complete, Vilsmeier formylation is carried out according toknown procedures. For that purpose the phenyl ether is dissolved in DMFor toluene or xylene etc. (or a mixture of solvents) and reacted withphosphorus oxychloride and an N,N-dialkylated amide, e.g. DMF ordimethylformanilide. After stirring for several hours at a temperatureof from −10° C. to 60° C., hydrolysis is carried out and thebenzaldehyde is isolated.

[0055] Depending upon the phenol, the reaction sequence can also takeplace in the reverse order (reaction step (1b)).

[0056] The preparation of the phenylethylamines (reaction step (2)) iscarried out according to the so-called Henry reaction. For that purpose,the aldehyde prepared in reaction step (1a) or (1b) is heated forseveral hours, at from 30° C. to 100° C., with a mixture of ammoniumacetate and a nitroalkane in a suitable solvent. The yellow nitrostyreneformed is then hydrogenated catalytically. For that purpose, thenitrostyrene is dissolved in a suitable solvent, e.g. ethanol, methanol,THF, dioxane or a mixture of solvents, and reduced for several hours ina hydrogenation autoclave under a hydrogen atmosphere of from 1 to 10bar using a catalyst and at from −15 to 50° C. with the addition of asuitable acid, e.g. hydrochloric acid or sulfuric acid. Thephenylethylamine is isolated in hydrochloride or hydrosulfate form.

[0057] Alternatively, the nitrostyrene can be reduced with LiAIH₄ in asuitable solvent, e.g. diethyl ether, tert-butyl methyl ether or THF, ata temperature of from −45 to 65° C. to form the correspondingphenylethylamine. The hydrochlorides are obtained by dissolution of thephenylethylamines in an inert solvent and reaction with dry hydrogenchloride.

[0058] In particular, compounds (100)-(102) can be prepared according tothat process.

[0059] The phenylethylamine derivatives used according to the inventionexhibit pronounced antimicrobial action, especially against pathogenicgram-positive and gram-negative bacteria and against bacteria of theskin flora, and also against yeasts and moulds. They are accordinglysuitable especially for disinfection, deodorisation, and for general andantimicrobial treatment of the skin and mucosa and of integumentaryappendages (hair), more especially for the disinfection of hands andwounds.

[0060] They are accordingly suitable as antimicrobial active ingredientsand preservatives in personal care preparations, such as shampoos, bathadditives, haircare preparations, liquid and solid soaps (based onsynthetic surfactants and salts of saturated and/or unsaturated fattyacids), lotions and creams, deodorants, other aqueous or alcoholicsolutions, e.g. cleansing solutions for the skin, moist cleansingcloths, oils or powders.

[0061] The invention accordingly relates also to a personal carepreparation comprising at least one compound of formula (1) andcosmetically tolerable carriers or adjuvants.

[0062] The personal care preparation according to the invention containsfrom 0.01 to 15% by weight, preferably from 0.1 to 10% by weight, basedon the total weight of the composition, of a compound of formula (1),and cosmetically tolerable adjuvants.

[0063] Depending upon the form of the personal care preparation, itcomprises, in addition to the phenylethylamine derivative of formula(1), further constituents, such as sequestering agents, colourings,perfume oils, thickening or solidifying (consistency regulator) agents,emollients, UV-absorbers, skin protective agents, antioxidants,additives that improve the mechanical properties, such as dicarboxylicacids and/or aluminium, zink, calcium or magnesium salts of C₁₄-C₂₂fattyacids, further antimicrobials and, optionally, preservatives.

[0064] Typical antimicrobials for combination phenylethylaminoderivatives are:

[0065] formaldehyde and paraformaldehyde;

[0066] hydroxy biphenyls and their salts such as ortho-phenylphenol;

[0067] zinc pyrithion;

[0068] chlorobutanol;

[0069] hydroxy benzoic acids and their salts and esters such as methylparaben, ethyl paraben, propyl paraben, butyl paraben;

[0070] dibromo hexamidine and its salts including isethionate(4,4′-hexamethylenedioxy-bis(3-bromo-benzamidine) and4,4′-hexamethylenedioxy-bis(3-bromo-benzamidinium2-hydroxyethanesulfonate);

[0071] mercury, (aceto-O)phenyl (i.e. phenyl mercuric acetate) andmercurate(2-),(orthoboate(3-)-O)phenyl, dihydrogen (i.e. phenyl mercuricborate);

[0072] 1,3-bis(2-ethylhexyl)-hexahydro-5-methyl-5-pyrimidine(hexetidin);

[0073] 5-bromo-5-nitro-1,3-dioxan;

[0074] 2-bromo-2-nitro-1,3-propanediol;

[0075] 2,4-dichlorobenzyl alcohol;

[0076] 3,4,4′ trichlorocarbanilide (trichlorcarban);

[0077] p-chloro-m-cresol;

[0078] 2,4,4′-trichloro-2-hydroxydiphenylether (triclosan);

[0079] 4,4′-dichloro-2-hydroxydiphenylether;

[0080] 4-chloro-3,5-dimethylphenol (chloroxylenol);

[0081] imidazolidinyl urea;

[0082] poly-(hexamethylene biguanide) hydrochloride;

[0083] 2-phenoxy ethanol (phenoxyethanol);

[0084] hexamethylene tetramine (methenamine);

[0085] 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamantane chloride(quaternium 15);

[0086] 1-(4-chlorophenyoxy)-1-(1-imidazolyl)3,3-dimethyl-2-butanone(climbazole);

[0087] 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione (DMDMhydantoin);

[0088] benzyl alcohol;

[0089] 1,2-dibromo-2,4-dicyano butane;

[0090] 2,2′ methylene-bis(6-bromo-4-chloro phenol) (bromochlorophene);

[0091] methylchloroisothiazolone, methylisothiazolone,octylisothiazolone, benzylisothiazolone;

[0092] 2-benzyl-4-chlorophenol (chlorophenone);

[0093] chloracetamide;

[0094] chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate,chlorhexidine hydrochloride;

[0095] 1-phenoxy-propane-2-ol (phenoxyisopropanol);

[0096] 4,4-dimethyl-1,3-oxazolidine (dimethyl oxazolidine);

[0097] diazolidinyl urea;

[0098] 4,4′-hexamethylenedioxybisbenzamidine and4,4′-hexamethylenedioxybis-(benzamidinium-2-hydroxyethanesulfonate);

[0099] glutaraldehyde (1,5-pentanedial);

[0100] 7-ethylbicyclooxazolidine;

[0101] 3-(4-chlorophenoxy)-1,2-propanediol (chlorophenesin);

[0102] phenylmethoxymethanol and ((phenylmethoxy)methoxy)-methanol(benzylhemiformal)

[0103] N-alkyl(C₁₂-C₂₂)trimethyl ammoniumbromide and -chloride(cetrimonium bromide, cetrimonium chloride);

[0104]benzyl-dimethyl-(4-(2-(4-(1,1,3,3-tetramethylbutyl)-phenoxy)-ethoxy)-ethyl)-ammoniumchloride(benzethonium chloride);

[0105] alkyl-(C₈-C₁₈)-dimethyl-benzylammonium chloride, -bromide andsaccharinate;

[0106] (benzalkonium chloride, benzalkonium bromide, benzalkoniumsaccharinate);

[0107] benzoic acid and its salts and esters;

[0108] propionic acid and its salts;

[0109] salicylic acid and its salts;

[0110] sorbic acid and its salts;

[0111] sodium iodate;

[0112] inorganic sulfites and bisulfites such as sodium sulfite;

[0113] dehydroacetic acid;

[0114] formic acid;

[0115] mercurate(1-ethyl)2-mercaptobenzoate(2-)-O,S-,hydrogene(thiomersal or thiomerosal);

[0116] 10-undecylenic acid and its salts;

[0117] octopirox (piroctone olamine);

[0118] sodium hydroxy methyl-aminoacetate (sodiumhydroxymethylglycinate);

[0119] 3-iodo-2-propynyl butylcarbamate.

[0120] The personal care preparation according to the invention may bein the form of a water-in-oil or oil-in-water emulsion, an alcoholic oralcohol-containing formulation, a vesicular dispersion of an ionic ornon-ionic amphiphilic lipid, a gel, a solid stick or an aerosolformulation.

[0121] As a water-in-oil or oil-in-water emulsion the cosmeticallytolerable adjuvant contains preferably from 5 to 50% of an oil phase,from 5 to 20% of an emulsifier and from 30 to 90% water. The oil phasemay comprise any oil suitable for cosmetic formulations, for example oneor more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fattyacid ester or a fatty alcohol. Preferred mono- or poly-ols are ethanol,isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.

[0122] Typical surfactant formulations for cleaning and disinfectingskin, hair, mucous membranes and inanimate surfaces (including textilecare) may contain the following ingredients:

[0123] anionic, non-ionic, amphoteric, or cationic surfactants;

[0124] anionic surfactants can be sulfates such as fatty alcoholsulfates, e.g. sulfated laurylalcohol, fatty acohol ether sulfates suchas the acidic esters or their salts of a polymer with 2 to 30 Molethylene oxide per mole of a C₈-C₂₂-fatty alcohol, alkali metals and/orammonium salts and/or amine salts of C₈-C₂₀fatty acids, alkylamidesulfates, alkylamine sulfates (such as monoethanolamine lauryl sulfate),alkylamide ethersulfates, alkylarylpolyethersulfates, monoglyceridesulfates, alkane sulfonates such as those containing alkyl chains with 8to 20 carbon atoms (e.g. dodecyl sulfonate), alkylamide sulfonates,alkylarylsulfonates, α-olefine sulfonates, sulfosuccinate derivatives(e.g. alkyl sulfosuccinate, alkylethersulfosuccinate oralkylsulfosuccinamide derivatives);

[0125] N-[alkylamidoalkyl]amino acids of formula

[0126] wherein X is a hydrogen, C₁-C₄-alkyl or —COO⁻M⁺, Y is a hydrogenor C₁-C₄-alkyl, Z is —(CH₂)_(m) ₁ ⁻¹; m₁ is 1 to 5, n₁ is a number of 6to 18 and M is an alkali metal- or amine cation;

[0127] alkyl- and alkylaryl ethercarboxylates of the formula CH₃—X—Y—A,with X is a chain with the general formula —(CH₂)₅₋₁₉—O—,

[0128] R is a hydrogen or C₁-C₄-alkyl, Y is —(CHCHO)₁₋₅₀—,A is(CH₂)_(m2-1)—COO⁻M⁺or

[0129] m₂ is a number of 1 to 6 and M is an alkali metal- or aminecation.

[0130] Moreover anionic surfactants can be fatty acid methyl tauride,alkylisothionate, fatty acid polypeptide condensation products and fattyalcohol phosphoric acid esters. The alkyl radicals in the compoundsmentioned above have a C-atom number of typically 8 to 24.

[0131] Anionic surfactants are usually used as water-soluble salts suchas alkali metal salts, ammonium salts or amine salts. Examples for suchsalts are lithium salts, sodium salts, potassium salts, ammonium salts,triethanolamine salts, ethanolamine salts, diethanolsamine salts andothers.

[0132] Particularly the sodium salt, potassium salt and ammonium(NR₁R₂R₃)-salt is preferred. R₁, R₂ and R₃ can be hydrogen, C₁-C₄-alkylor C₁-C₄-hydroxyalkyl.

[0133] Of particular interest for the formulations are monoethanolaminelaurylsulfate or alkali metal salts of fatty alcohol sulfates such assodium laurylsulfate and sodium laurylethersulfate.

[0134] As amphoteric surfactants C₈-C₁₈-betains, C₈-C₁₈-sulfobetains,C₈-C₂₄-alkylamido-C₁-C₄-alkylene betains, imidazoline carboxylates,alkylamphocarboxycarboxylic acids, alkylamphocarboxylic acid (e.g.lauroamphoglycinate) and N-alkyl-β-aminopropionate or -iminodipropionatecan be used.

[0135] In particular the C₁₀-C₂₀-alkylamidoC₁-C₄-alkylenbetaine and cocofatty acid amide propylbetaine.

[0136] Non-ionic surfactants can be e.g. derivatives of adducts ofpropylene oxide/ethylene oxide with a molecular weight of 1,000 to15,000, fatty alcoholethoxylates (1-50 EO), alkyl-phenolpolyglycolethers(1-50 EO), polyglucosides, ethoxylated hydrocarbons, fatty acidgly-col(partial)esters such as diethylenglycolmonostearate, fatty acidalkanolamides and -dialkanolamides, fatty acid alkanolamide ethoxylatesand fatty amineoxides.

[0137] Moreover the salts of saturated and unsaturated C₈-C₂₂-fattyacids, alone or in combinations with other substances of this group orcombinations with other surfactants mentioned above, can be used.

[0138] Examples of those fatty acids are capric acid, lauric acid,myristic acid, myristinic acid, palmitic acid, stearic acid, arachidicacid, behenic acid, caproleinic acid, dodecenoic acid, tetradecenoicacid, octadecenoic acid, oleic acid, eicosenic acid, erucic acid as wellas combinations thereof such as coco fatty acid. The acids can be usedin their salt form, e.g. as alkali metal salts such as sodium salts,potassium salts, or metal salts such as Zn and/or aluminium salts orother alkaline reacting , nitrogen-containing organic compounds such asamines or ethoxylated amines.

[0139] These salts can be also produced in situ.

[0140] Typical product types are gels (aqueous gels and oleogels),emulsions (w/o systems, o/w systems, water in silicone systems),microemulsions, multiple emulsions (o/w/o and w/o/w systems), sprays(with and without alcohol), sticks (based on synthetic and/or naturalsoaps), powders, anhydrous creams, oils etc.

[0141] Such formulations for personal care, household and laundry careapplications may contain raw materials such as preservatives,bactericides and bacteriostatic agents (see list above), perfumes,anti-foaming agents, dyes, pigments, thickening agents, moisturizingagents, humectants, fats, oils, waxes or other typical ingredients ofcosmetic and personal care formulations as well as of household productsand laundry care products such as alcohols, poly-alcohols, polymers,foam stabilizers, electrolytes, organic solvents, silicone derivatives,emollients, emulsifiers, surfactants, UV absorbers, antioxidants,anti-irritants and anti-inflammatory agents etc.

[0142] Antioxidants can be amino acids or amino acid derivatives,imidazoles and their derivatives, peptides such as D,L-carnosine,carotinoids, caroteines and their derivatives, liponic acid, metalchelating agents (such as alpha-hydroxy fatty acids, palmitic acid,phytic acid, lac-toferrine), alpha-hydroxyacids (e.g. citric acid,lactic acid, maleic acid), humic acid, gallate, EDTA, EGTA and theirderivatives, unsaturated fatty acids and their derivatives, vitamin Cand its derivatives, rutinic acid and its derivatives, alpha-glycosylrutin, ferulic acid, butylhydroxytoluene, butylhydroxyanisole andsuitable derivatives of these substances.

[0143] Moreover an antioxidant in such formulations might betetradibutyl pentaerithrityl hydroxy-hydrocinnamate (Tinogard™ TT).

[0144] UV absorbers in the formulations might be benzophenone-typesubstances such as benzophenone-1, benzophenone-2, benzophenone-3 orbenzophenone-4 or benzotriazol-type substances such as:

[0145] benzenesulfonic acid,3-(2H-benzotriazol-2-yl)-4-hydroxy-5-(1-methylpropyl)-, monosodium salt;

[0146]2-(5-chloro-2H-benzotriazol-2-yl)-6-(1,1-dimethylethyl)-4-methyl-phenol(i.e. bumetrizole);

[0147] 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methyl-phenol, branched andlinear.

[0148] In emulsions, typical emulsifiers used are:

[0149] carboxylic acids and their salts such as palmitinic acid, stearicacid, oleic acid, lauric acid etc.;

[0150] alkyl phosphates or phosphoric acid esters such as diethanolaminecetyl phosphate, potassium cetyl phosphate etc.;

[0151] alkylamines;

[0152] alkyl imidazolines;

[0153] ethoxylated amines;

[0154] quaternary emulsifiers;

[0155] sorbitol and sorbitan (polysorbates, sorbitan esters);

[0156] sucrose and glucose derivatives such as sorbitan stearate,sucrose cocoate, methyl glucose-sesquistearate, methyl glucose dioleate,methyl glucose isostearate;

[0157] alkanolamides and ethoxylated amides such as PEG-n acylamides(with n=1-50);

[0158] ethoxylated carboxylic acids or polyethylene glycol esters (PEG-nacylates with n=1-200) such as fatty alcohol polyglycolethers, laureth-n(with n=1-200) ceteareth-n (with n=1-200), -steareth-n (with n=1-100),oleth-n (with n=1-200) and PEG-n stearate (with n=1-200), -PEG-n oleate(with n=1-200), PEG-n cocoate (with n=2-150)

[0159] polyglyceryl esters and fatty acid esters;

[0160] dimethicone copolyols such as silicone polyethylene oxidecopolymer, silicone glycol copolymer;

[0161] propoxylated or polyoxyethylene ethers;

[0162] polaxamers;

[0163] polymeric emulsifiers such as acrylate copolymers orcrosspolymers and acrylamides or polyacrylamides;

[0164] The lipid phase can be chosen from the following substancegroups:

[0165] mineral oils, mineral waxes;

[0166] oils such as triglycerides of capric and caprylic acid, naturaloils such as castor oil;

[0167] fats, waxes and other natural and synthetic fats e.g. esters offatty acids with short chain alcohols such as isopropanol, propyleneglycol or glycerin, or esters of fatty alcohols with fatty acids orcarboxylic acids with low number of carbon atoms;

[0168] alkyl benzoates;

[0169] silicone oils such as dimethylpolysiloxane, diethylpolysiloxane,diphenylpolysiloxane or mixtures thereof;

[0170] The oil phase of emulsions, oleogels, hydrodispersions orlipodispersions can be chosen

[0171] from the group of esters of saturated and/or unsaturated,branched and/or linear alkane carboxylic acids with a chain length of 3to 30 C-atoms and saturated and/or unsaturated, branched or linearalcohols with a chain length of 3 to 30 C-atoms;

[0172] from the group of esters of aromatic carboxylic acids andsaturated and/or unsaturated, branched and/or linear alcohols with achain length of 3-30 C-atoms.

[0173] Examples of such ester oils are isopropylmyristate,isopropylpalmitate, isopropylstearate, iso-propyloleate,n-butylstearate, n-hexyllaurate, n-decyloleate, isooctylstearate,iso-nonylstearate, isononylisononanoate, 2-ethylhexylpalmitate,2-hexyllaurate, 2-hexyldecylstearate, 2-octyidodecylpalmitate,oleyloleate, oleylerucate, erucyloleate, erucylerucate as well assynthetic, semi-synthetic and natural mixtures of such esters such asjojoba oil.

[0174] The oil phase can be also chosen from the group of saturated andunsaturated hydrocarbons and waxes, silicone oils, dialkylethers, thegroup of saturated, unsaturated, linear or branched alcohols, fatty acidtriglyerides e.g. triglycerin esters of saturated and/or unsaturated,linear and/or branched alkane carboxylic acids with a chain length of8-24 C-atoms, particularly 12 to 18 C-atoms.

[0175] The fatty acid triglycerides can be chosen from the groups ofsynthetic, semi-synthetic and natural oils e.g. olive oil, sunfloweroil, soy oil, peanut oil, rape-seed oil, palm oil, almond oil, coconutoil and similar oils.

[0176] Mixtures of such oil and wax components or waxes such as cetylpalmitate can be used as sole oil phase.

[0177] Other preferred ingredients in the oil phase are from the groupof 2-ethylhexylisostearate, octyidodecanol, isotridecylisononanoate,isoeicosane, 2-ethylhexylcocoate, C₁₂-C₁₅-alkyl benzoate,caprylic-capric acid-triglycerides and dicaprylic ether or mixtures ofthose ingredients such as mixtures of 2-ethylhexylisostearate withC₁₂-C₁₅alkylbenzoate, mixtures of C₁₂-C₁₅ alkylbenozate andisotridecylisononanoate and mixtures of C₁₂-C₁₅ alkylbenozate with2-ethylhexylisostearate and isotridecylisononanoate. Moreover cyclic orlinear silicone oils can be used and are in some cases the onlyingredient in the oil phase. A preferred silicone oil is cyclomethicone(octamethylcyclotetrasiloxane), hexamethylcyclotrisiloxane,polydimethylsiloxane and poly(methylphenylsiloxane).

[0178] From the hydrocarbons the groups of paraffin oil, squalane andsqualene are preferred.

[0179] The aqueous phase contains for example ingredients such as

[0180] alcohols, diols or polyols with a low number of C-atoms or theirethers (e.g. ethanol, isopropanol, propyleneglycol, glyerin, ethyleneglycol, ethylene glycol monoethylether, ethylene glycol monobutylether,propylene glycol monomethylether, propylene glycol monoethylether,propylene glycol monobutylether, diethylene glycol monomethylether;diethylene glycol monoethylether, diethylene glycol monobutylether andsimilar products).

[0181] lower homologues of alcohols such as ethanol, isopropanol,1,2-dipropanediol, glycerine as well as one or more thickeners forexample of the groups of silicon dioxide, aluminium silicates,polysaccharides or derivatives thereof for example hyaluronic acid,xanthan gum, hydroxypropylmethylcellulose, polyacrylates e.g. substancesfrom the Carbopol range (e.g. Carbopol types 980, 981, 1 382, 2984,5984) or Salcare range (Salcare SC80, Salcare SC81, Salcare SC91,Salcare AST, Salcare SC 92, Salcare SC95, Salcare SC96).

[0182] Cosmetic formulations according to the invention are used invarious fields. There come into consideration, for example, especiallythe following preparations:

[0183] skin-care preparations, e.g. skin-washing and cleansingpreparations in the form of tablet-form or liquid soaps, soaplessdetergents or washing pastes,

[0184] bath preparations, e.g. liquid (foam baths, milks, showerpreparations) or solid bath preparations, e.g. bath cubes and bathsalts;

[0185] skin-care preparations, e.g. skin emulsions, multi-emulsions orskin oils;

[0186] cosmetic personal care preparations, e.g. facial make-up in theform of day creams or powder creams, face powder (loose or pressed),rouge or cream make-up, eye-care preparations, e.g. eyeshadowpreparations, mascara, eyeliner, eye creams or eye-fix creams; lip-carepreparations, e.g. lipsticks, lip gloss, lip contour pencils, nail-carepreparations, such as nail varnish, nail varnish removers, nailhardeners or cuticle removers;

[0187] intimate hygiene preparations, e.g. intimate washing lotions orintimate sprays;

[0188] foot-care preparations, e.g. foot baths, foot powders, footcreams or foot balsams, special deodorants and antiperspirants orcallous-removing preparations;

[0189] light-protective preparations, such as sun milks, lotions, creamsor oils, sun-blocks or tropicals, pre-tanning preparations or after-sunpreparations;

[0190] skin-tanning preparations, e.g. self-tanning creams;

[0191] depigmenting preparations, e.g. preparations for bleaching theskin or skin-lightening preparations;

[0192] insect-repellents, e.g. insect-repellent oils, lotions, sprays orsticks;

[0193] deodorants, such as deodorant sprays, pump-action sprays,deodorant gels, sticks or roll-ons;

[0194] antiperspirants, e.g. antiperspirant sticks, creams or roll-ons;

[0195] preparations for cleansing and caring for blemished skin, e.g.soapless detergents (solid or liquid), peeling or scrub preparations orpeeling masks;

[0196] hair-removal preparations in chemical form (depilation), e.g.hair-removing powders, liquid hair-removing preparations, cream- orpaste-form hair-removing preparations, hair-removing preparations in gelform or aerosol foams;

[0197] shaving preparations, e.g. shaving soap, foaming shaving creams,non-foaming shaving creams, foams and gels, preshave preparations fordry shaving, aftershaves or aftershave lotions;

[0198] fragrance preparations, e.g. fragrances (eau de Cologne, eau detoilette, eau de parfum, parfum de toilette, perfume), perfume oils orperfume creams;

[0199] dental care, denture-care and mouth-care preparations, e.g.toothpastes, gel tooth-pastes, tooth powders, mouthwash concentrates,anti-plaque mouthwashes, denture cleaners or denture fixatives;

[0200] cosmetic hair-treatment preparations, e.g. hair-washingpreparations in the form of shampoos and conditioners, hair-carepreparations, e.g. pretreatment preparations, hair tonics, stylingcreams, styling gels, pomades, hair rinses, treatment packs, intensivehair treatments, hair-structuring preparations, e.g. hair-wavingpreparations for permanent waves (hot wave, mild wave, cold wave),hair-straightening preparations, liquid hair-setting preparations, hairfoams, hairsprays, bleaching preparations, e.g. hydrogen peroxidesolutions, lightening shampoos, bleaching creams, bleaching powders,bleaching pastes or oils, temporary, semi-permanent or permanent haircolourants, preparations containing self-oxidising dyes, or natural haircolourants, such as henna or camomile.

[0201] An antimicrobial soap has, for example, the followingcomposition:

[0202] 0.01 to 5% by weight of a compound of formula (1)

[0203] 0.3 to 1% by weight titanium dioxide,

[0204] 1 to 10% by weight stearic acid,

[0205] ad 100% soap base, e.g. a sodium salt of tallow fatty acid orcoconut fatty acid, or glycerol.

[0206] A shampoo has, for example, the following composition:

[0207] 0.01 to 5% by weight of a compound of formula (1),

[0208] 12.0% by weight sodium laureth-2-sulfate,

[0209] 4.0% by weight cocamidopropyl betaine,

[0210] 3.0% by weight NaCl and

[0211] water ad 100%.

[0212] A deodorant has, for example, the following composition:

[0213] 0.01 to 5% by weight of a compound of formula (1),

[0214] 60% by weight ethanol,

[0215] 0.3% by weight perfume oil, and

[0216] water ad 100%.

[0217] The invention relates also to an oral composition comprising from0.01 to 15% by weight, based on the total weight of the composition, ofa compound of formula (1), and orally tolerable adjuvants.

[0218] Example of an oral composition:

[0219] 10% by weight sorbitol,

[0220] 10% by weight glycerol,

[0221] 15% by weight ethanol,

[0222] 15% by weight propylene glycol,

[0223] 0.5% by weight sodium lauryl sulfate,

[0224] 0.25% by weight sodium methylcocyl taurate,

[0225] 0.25% by weight polyoxypropylene/polyoxyethylene block copolymer,

[0226] 0.10% by weight peppermint flavouring,

[0227] 0.1 to 0.5% by weight of a compound of formula (1), and

[0228] 48.6% by weight water.

[0229] The oral composition according to the invention may be, forexample, in the form of a gel, a paste, a cream or an aqueouspreparation (mouthwash).

[0230] The oral composition according to the invention may also comprisecompounds that release fluoride ions which are effective against theformation of caries, for example inorganic fluoride salts, e.g. sodium,potassium, ammonium or calcium fluoride, or organic fluoride salts, e.g.amine fluorides, which are known under the trade name Olafluor.

[0231] The phenylethylamino derivatives have a strong antimicrobialactivity against oral bacteria and exhibit an anti-plaque effectiveness,anti-gingivitis activities and help to reduce paradentitis.

[0232] The activity can be improved by combinations with otherantimicrobial actives or anti-plaque and anti-gingivitis actives such aschlorhexidine, quaternary compounds such as cetrimonium bromide,benzalkonium chloride and/or phenolic substances such as 2,4,4′trichloro 2′-hydroxy diphenylether, 4,4′-dichloro 2-hydroxydiphenylether, thymol, and other phenolic compounds having the followinggeneric formula:

[0233] wherein R₂, R₃ and R₄ are independently from each other alkyl(branched, cyclo or linear), aryl, O-aryl, O-alkyl (linear, cyclo, orbranched).

[0234] Examples are e.g. thymol,2-tert.-butyl-5-(4-tert.-butylphenyl)-phenol, 2,4-di-t-butyl phenol,2-cyclohexylmethyl-4-t-butylphenol, 2-t-octyl-5-cyclohexylmethylphenol,2-t-butyl-4-(1,1-dimethylpropyl)phenol,2-t-butyl-4-(1,1-dimethylbutyl)phenol, 2,4-di-t-butyl-5-methylphenol,2-t-butyl-4-(1,1,2,2-tetramethylpropyl)-5-methylphenol,2-t-butyl-4-(1,1,2,2-tetramethylpropyl)phenol,2-t-butyl-5-cyclohexylmethylphenol, 2-t-butyl-4-n-heptylphenol,2-isopropyl-5-cyclohexylmethylphenol,2-isopropyl-4-cyclohexylmethylphenol, 2-cyclohexyl-4-n-heptylphenol.

[0235] Typical oral compositions containing the hydroxy diphenylethersalone or in combinations with one or more of the above mentionedantimicrobials and anti-plaque agents are e.g. mouthrinses, semi-solidssuch as toothpastes or gel dentifrices, chewing gums or solid lozengesor the like.

[0236] Such oral compositions may contain a phenylethylamine derivativeor a combination of a phenylethylamine derivative and one or more of theabove mentioned antimicrobial and/or anti-plaque compounds.

[0237] Furthermore the oral composition may contain:

[0238] polishing agents such as silica gels, colloidal silica or complexamorphous alkali metal alu-minosilicate, sodium bicarbonate, sodiummetaphosphate, potassium metaphosphate, tri-calcium phosphate,dehydrated dicalcium phosphate, anhydrous dicalcium phosphate, calciumpyrophosphate, calcium carbonate, aluminium silicate, hydrated alumina,silica, bentonite and mixtures thereof;

[0239] humectants such as glycerin, sorbitol, an alkylene glycol such aspolyethylene glycol or propylene glycol and mixtures thereof;

[0240] water;

[0241] natural or synthetic thickener or gelling agent such as irishmoss, iota-carrageenan, kappa-carrageenan, gum tragacanth, starch,polyvinylpyrrolidone, hydroxyethyl propyl cellulose, hydroxybutyl methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose andsodium carboxymethyl cellulose;

[0242] alcohol such as ethanol or isopropanol;

[0243] organic surface-active agents which can be cationic, anionic ornon-ionic;

[0244] Typical anionic surface-active agents are water-soluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglycerides of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2-dihydroxy propanesulfonate, and the substantially saturated higher aliphatic acyl amidesof lower aliphatic amino carboxylic acid compounds, such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals and alkoyltaurines, and the like.

[0245] Examples of the last mentioned amides and taurates are N-lauroylsarcosine, and the sodium, potassium and ethanolamine salts ofN-lauroyl, N-myristoyl, or N-palmitoyl sarcosine which should besubstantially free from soap or similar higher fatty acid material aswell as N-methyl-N-cocoyl (or oleoyl or palmitoyl) taurines.

[0246] Typical nonionic surface-active agents are condensation productsof ethylene oxide with various reactive hydrogen-containing compoundsreactive therewith having long hydrophobic chains (e.g. aliphatic chainsof about 12-20 carbon atoms), which condensation products (“ethoxamers”)contain hydrophilic polyoxyethylene moieties, such as condensationproducts of poly(ethyleneoxide) with fatty acids, fatty alcohols, fattyamides, polyhydric alcohols (e.g. sorbitan monostearate) andpolypropylene oxide (e.g. Pluronic® materials). Polyoxamers are e.g.block copolymers of polyoxyethylene and polyoxypropylene having anaverage molecular weight from about 3000 to 5000 and a preferred averagemolecular weight from about 3500 to 4000 and containing about 10-80%hydrophilic polyoxyethylene groups, by weight, of the block copolymer(e.g. Pluronic F127).

[0247] flavoring agents such as flavoring oils, e.g. oil of spearmint,peppermint, wintergreen, sassafras, clove, sage, eucalyptus, cinnamon,lemon, orange and methyl salicylate.

[0248] sweetening agents such as sucrose, lactose, maltose, xylitol,sodium cyclamate, perillartine, aspartyl phenyl alanine methyl ester,saccharine and the like;

[0249] agents used to diminish teeth sensitivity such as strontiumchloride, potassium nitrate and potassium citrate;

[0250] whitening agents such as urea peroxide and hydrogen peroxide;

[0251] preservatives such as sodium benzoate;

[0252] substances which release fluoride ions to protect against cariessuch as inorganic fluoride salts, e.g. sodium, potassium, ammonium orcalcium fluoride or organic fluorides such as amine fluoride;

[0253] other agents such as chlorophyll compounds and/orammonium-containing materials such as urea, diammonium phosphate andmixtures thereof.

[0254] Antibacterial enhancing agents may be included in the oralcomposition. Such antibacterial enhancing agents contain adelivery-enhancing group (attaches or substantively, adhesively,cohesively or otherwise bonds the antibacterial enhancing agents withthe antibacterial and/or anti-plaque agent to the oral (e.g. tooth andgum) surface) and a retention-enhancing group (generally a hydrophobicgroup which attaches or otherwise bonds the antimicrobial and/oranti-plaque agent to the antibacterial enhancing agent).

[0255] These substances thus deliver the antimicrobial and/or antiplaqueagent to the surface and promote retention of the active on the surfacewhich improves the retardation of plaque growth on oral surfaces.

[0256] Preferably, the antibacterial enhancing agent is an anionicpolymer comprising a chain or backbone containing repeating units eachpreferably containing at least one carbon atom and preferably at leastone directly or indirectly pendent, monovalent delivery-enhancing groupand at least one directly or indirectly pendent monovalentretention-enhancing group geminally, vicinally or less preferablyotherwise bonded to atoms, preferably carbon, in the chain.

[0257] The antibacterial enhancing agent may be a single compound,preferably a polymerizable monomer, more preferably a polymer, includingfor example oligomers, homopolymers, copolymers, of two or moremonomers, ionomers, block copolymers, graft polymers, cross-linkedpolymers and copolymers, and the like. The antibacterial enhancing agentmay be natural or synthetic, and water-soluble or preferablywater(saliva)-soluble or -swellable (hydratable, hydrogel-forming)having a (weight) average molecular weight of about 100 to about5,000,000, preferably about 1000 to about 1,000,000, more preferablyabout 25,000 to 500,000.

[0258] The phenylethylamine derivatives of formula (1) used according tothe invention are also suitable for treating, especially preserving,textile fibre materials. Such materials are undyed and dyed or printedfibre materials, e.g. of silk, wool, polyamide or polyurethanes, andespecially cellulosic fibre materials of all kinds. Such fibre materialsare, for example, natural cellulose fibres, such as cotton, linen, juteand hemp, as well as cellulose and regenerated cellulose. Preferredsuitable textile fibre materials are made of cotton.

[0259] The phenylethylamine derivatives according to the invention aresuitable also for treating, especially imparting antimicrobialproperties to or preserving, plastics, e.g. polyethylene, polypropylene,polyurethane, polyester, polyamide, polycarbonate, latex, etc.. Fieldsof use therefor are, for example, floor coverings, plastics coatings,plastics container and packaging materials; kitchen and bathroomutensils (e.g. brushes, shower curtains, sponges, bathmats), latexfilter materials (air and water filters), plastics articles used in thefield of medicine, e.g. dressing materials, syringes, catheters etc.,so-called “medical devices”, gloves and mattresses.

[0260] Paper, for example papers used for hygiene purposes, may also beprovided with antimicrobial properties using the phenylethylaminederivatives according to the invention.

[0261] It is also possible for nonwovens, e.g. nappies/diapers, sanitarytowels, panty liners, and cloths for hygiene and household uses, to beprovided with antimicrobial properties in accordance with the invention.

[0262] The phenylethylamine derivatives of formula (1) are also used inwashing and cleaning formulations, e.g. in liquid or powder washingagents or softeners.

[0263] The phenylethylamine derivatives of formula (1) can be usedespecially in household and general-purpose cleaners for cleaning anddisinfecting hard surfaces.

[0264] A cleaning preparation has, for example, the followingcomposition:

[0265] 0.01 to 5% of a compound of formula (1)

[0266] 3.0% octyl alcohol 4EO

[0267] 1.3% fatty alcohol C₈-C₁₀polyglucoside

[0268] 3.0% isopropanol

[0269] ad 100% water.

[0270] In addition to preserving cosmetic and household products, thepreservation of technical products, the provision of technical productswith antimicrobial properties and use as a biocide in technicalprocesses are also possible, for example in paper treatment, especiallyin paper treatment liquors, printing thickeners of starch or ofcellulose derivatives, surface-coatings and paints.

[0271] Combinations with chelating agents can also improve theantimicrobial activity of hydroxy diphenylethers. Examples of suchchelating agents resulting in additional antimicrobial effects orsynergistic activity when combined with hydroxy diphenylethers areethylene di-amine tetra acetic acid (EDTA), beta-alanine diacetic acid(EDETA), hydroxyethylene di-amino tetraacetic acid, nitrilotriaceticacid (NTA) and ethylenediamine disuccinic acid (S,S-EDDS, R,R-EDDS orS,R-EDDS).

[0272] Also combinations of hydroxy diphenylethers such as 4-(2-tert.butyl-5-methylphenoxy)-phenol with perfumes, particularly thosecontaining plant-derived oils, can result in a better antimicrobialefficacy.

[0273] Also combinations with natural antimicrobials or chemicallymodified natural substances with antimicrobial activities such aschitosans and chitosan derivatives, farnesol, plant extracts such asclove oil, blue cypress oil etc. can result in additional antimicrobialeffects or even synergistic activities.

[0274] The phenylethylamine derivatives of formula (1) are also suitablefor the antimicrobial treatment of wood and for the antimicrobialtreatment of leather, the preserving of leather and the provision ofleather with antimicrobial properties.

[0275] The compounds according to the invention are also suitable forthe protection of cosmetic products and household products frommicrobial damage.

[0276] The phenylethylamine derivatives that can be used according tothe invention are known compounds or new compounds.

[0277] The new compounds correspond to formula

[0278] wherein

[0279] R′₁, R′₂ and R′₃ are each independently of the others hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-, car- boxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- ordi-C₁-C₂₀alkylamino- or nitro-substituted phenyl or phenyl-C₁-C₅alkyl,naphthyl-C₁-C₅alkyl, phenylcarbonyl-C₁-C₅alkyl,naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl, furanylalkyl,thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl, oxazolylalkyl,thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl;

[0280] R′₄, R′₅, R′₆ and R′₇ are each independently of the othershydrogen; C₁-C₂₀alkyl; C₃-C₁₂-cycloalkyl; C₂-C₂₀alkenyl;C₄-C₁₂cycloalkenyl; C₃-C₂₀alkynyl; or C₄-C₁₂cycloalkynyl; an

[0281] m′ and n′ are each independently of the other 0 or 1,

[0282] but do not include those compounds of formula (1′) wherein

[0283] n′ is 1; and

[0284] m′ is 0; and simultaneously

[0285] R′₁ and R′₂ are C₁-C₅alkyl, C₂-C₅alkenyl; benzyl; or a radical offormula (1′a)

[0286] R′₈ is C₁-C₄alkyl;

[0287] R′₄, R′₅, R′₆ and R′₇ are hydrogen;

[0288] or those compounds of formula (1′) wherein

[0289] n′ and m′ are 1;

[0290] R′₁, R′₂ and R′₃ are benzyl; and

[0291] R′₄, R′₅, R′₆ and R′₇ are hydrogen.

[0292] The invention relates also to the compounds of formula (1′).

[0293] The following Examples illustrate the present invention but donot limit it in any way.

General Method for Loading Resin

[0294] The compounds of formulae (4) to (102) can be prepared asdescribed below.

EXAMPLE 1

[0295] A suspension of dopamine hydrochloride (1.35 g; 7.1 mmol) inabsolute dichloromethane (10 ml) and ethyldiisopropylamine (DIPEA, 36mmol; 5 eq.; 4.6 g; 6.1 ml) is cooled to 0° C. TMSCl (2.2 eq.; 15.6mmol; 1.69 g; 1.97 ml) is slowly added dropwise. After stirring for 1hour at 25° C., TCP resin (1.44 mmol/g; 0.3 eq.; 2.4 mmol; 1.67 g) isadded. The suspension is shaken for 20 hours at 25° C. Unreacted resinis separated off by the addition of methanol (5 ml). Suction-filtrationis then carried out, followed by washing with DMF, MeOH, THF, DCM andEt₂O. The resin is dried in vacuo for 1 hour.

EXAMPLE 2 Removal of the TMS Groups

[0296] In order to remove the TMS groups, the resin is shaken with asolution of tetrabutyl-ammonium fluoride (TBAF) (2 eq. based on resinloading; 4.8 mmol; 1.25 g) in THF (20 ml) for 1 hour at 25° C. The resinis washed and dried as described in Example 1.

EXAMPLE 3 Alkylation of the OH Groups

[0297] Method 1: 25 mg of the dopamine-loaded resin (36 μmol) aresuspended in dichloromethane (1 ml), and DIPEA (30 eq.; 1.08 mmol; 140mg; 185 μl) and alkyl halide (20 eq.; 720 μmol) are added. Shaking iscarried out for 16 hours at 25° C. and then the resin is washed asdescribed in Example 1. In order to complete the reaction, the procedureis repeated.

[0298] Method 2: 25 mg of the dopamine-loaded resin (36 μmol) aresuspended in DMF (1 ml), and BEMP (16 eq.; 576 μmol; 158 mg; 167 μl) andalkyl halide (16 eq.; 576 μmol) are added. Shaking is carried out for 24hours at 50° C. and then washing is carried out as described in Example1.

[0299] Method 3: 25 mg of the dopamine-loaded resin (36 μmol) aresuspended in absolute THF (2 ml), and triphenylphosphine (10 eq.; 360μmol; 95 mg) is added. Azodicarboxylic acid dipiperidide (10 eq.; 360μmol; 91 mg) and a suitable alcohol (12 eq.; 432 μmol) are then added.The mixture is shaken for 24 hours at 25° C. and then the resin iswashed as described in Example 1.

EXAMPLE 4 Isolation of the Products

[0300] 25 mg of the dopamine-loaded resin (36 μmol) are suspended in amixture of acetic acid/methanol/dichloromethane 2:2:6 (2 ml) and thesuspension is shaken for 5 hours at 25° C. The solution is filtered andthe filtrate is concentrated to dryness in vacuo. The residue is takenup in tert-butyl alcohol/water 4:1 and freeze-dried.

[0301] All the products are characterised by ESI-MS and HPLC and exhibitthe corresponding protonated products. Some of the compounds arecharacterised by means of ¹H- and ¹³C-NMR.

Results

[0302] Purity of the products [%] Method (HPLC 214 nm) Alkyl halideethyl iodide 1 94 isopentyl bromide 1 >90   isopentyl bromide 2 >99  allyl bromide 2 >99   Alcohol propanol 3 75 butanol 3 83 benzyl alcohol3 85 2-phenoxyethanol 3 74 2-phenylethanol 3 76

EXAMPLE 5 Liquid phase synthesis of2-(3,4,5-trisbenzyloxyphenyl)-ethylamine Reaction scheme

[0303]

[0304] Literature: A. R. Battersby et al. J. Chem. Soc. Perkin Trans.1981, 2016 and references cited therein.

EXAMPLE 5a 3.4,5-Trisbenzyloxybenzoic Acid Methyl Ester

[0305] 105 g (0.83 mol) of benzyl chloride are added dropwise at 56° C.,under reflux, over a period of 10 minutes, to 18.4 g (0.1 mol) of3,4,5-trihydroxybenzoic acid methyl ester, 50.0 g (0.48 mol) of sodiumcarbonate and 10.0 g (0.06 mol) of potassium iodide in 200 ml ofacetone. After a further 20 hours at reflux, 500 ml of water are addedat room temperature and the mixture is then extracted with ether. Thecrude product is worked up in customary manner, excess benzyl chlorideis removed by distillation, and the residue is recrystallised fromhexane/ethyl acetate. Colourless crystals, yield 45.0 g (98% of theory)

[0306]¹H-NMR (CDCl₃): 3.85 (s,3H, OCH₃), 5.05 (s, 2H, OCH₂), 5.10 (s,4H, OCH₂), 7.15-7.45 (m, 17H, arom. H)

EXAMPLE 5b 3,4,5-Trisbenzyloxybenzyl Alcohol

[0307] A solution of 20.0 g (0.044 mol) of 3,4,5-trisbenzyloxybenzoicacid methyl ester in 100 ml of THF is added dropwise with vigorousstirring, over a period of 60 minutes at room temperature, to asuspension of 4.00 g (0.11 mol) of lithium alanate in 100 ml of THF, inthe course of which the temperature rises to 65° C. (reflux). After afurther 2 hours at reflux, excess lithium alanate is cautiouslyhydrolysed, and the product is isolated in customary manner byextraction with methylene chloride. Amorphous powder, yield 12.0 g (64%of theory).

[0308]¹H-NMR (CDCl₂): 1.70 (t, 1H, OH), 4.45 (d, 2H, CH₂OH), 4.95 (s,2H, OCH₂), 5.00 (s, 4H, OCH₂), 6.55 (s, 2H, arom. H), 7.15-7.40 (m, 15H,arom. H)

EXAMPLE 5c 3,4,5-Trisbenzyloxybenzyl Chloride

[0309] 40.0 g (0.33 mol) of thionyl chloride are added dropwise at roomtemperature to a suspension of 12.0 g (0.028 mol) of3,4,5-trisbenzyloxybenzyl alcohol in 100 ml of diethyl ether. Heating isthen carried out at reflux for 2 hours, resulting in a clear solution.After removal of excess thionyl chloride and solvent, the residue isrecrystallised from isopropanol/hexane.

[0310] Colourless crystals, yield 8.0 g (64% of theory)

[0311]¹H-NMR (CDCl₃): 4.40 (s, 2H, CH₂Cl), 4.95 (s, 2H, OCH₂), 5.05 (s,4H, OCH₂), 6.60 (s, 2H, arom. H), 7.15-7.35 (m, 15H, arom. H)

EXAMPLE 5d 3,4,5-Trisbenzyloxyphenylacetonitrile

[0312] A mixture of 7.0 g (0.015 mol) of 3,4,5-trisbenzyloxybenzylchloride, 7.0 g (0.1 mol) of potassium cyanide and 1.8 g (0.01 mol) ofsodium iodide in 200 ml of acetone is heated at reflux for 18 hours withvigorous stirring. After cooling, 200 ml of water are added, and theproduct is extracted with chloroform. Recrystallisation from isopropanolyields colourless crystals.

[0313] Yield 2.0 g (30% of theory).

[0314] IR (KBr): v(CN)=2250 cm⁻¹

EXAMPLE 5e 2-(3,4,5-Trisbenzyloxvphenyl)-Ethylamine

[0315] At room temperature, first a solution of 1.0 g (0.0023 mol) of3,4,5-trisbenzyloxyphenyl-acetonitrile in 30 ml of THF, and then 10 ml(0.081 mol) of boron trifluoride-diethyl ether complex, are addeddropwise to a suspension of 2.5 g (0.067 mol) of sodium borohydride in20 ml THF. After 2 hours at reflux and cooling, 15 ml of 20%hydrochloric acid and 50 ml of water are added, extraction is carriedout with chloroform, and the extract is dried thoroughly with 4Amolecular sieve and concentrated by evaporation. After the residue hasbeen taken up in diethyl ether, the hydrochloride is isolated by theintroduction of hydrogen chloride.

[0316] Hydrochloride: colourless crystals, yield 0.6 g (60% of theory),purity 75% (LC, area % 54 nm), m.p.130° C.

[0317]¹H-NMR (free amine. CDCl₃): 2.80 (t, 2H, PhCH₂CH₂N), 3.05(S_(broad), 2H, PhCH₂CH₂N), 4.90 (s, 2H, OCH₂), 5.00 (s, 4H, OCH₂), 6.40(s, 2H, arom. H), 7.10-7.30 (m, 15H, arom. H), 8.15 (S_(broad), 2H, NH₂)

[0318] [M]+. m/z=439u

EXAMPLE 6

[0319] a) 4-Dodecyloxy-3-methoxybenzaldehyde

[0320] Vanillin (100 g; 0.657 mol) is dissolved in ethanol (500 ml), anddried K₂CO₃ (101.5 g; 0.73 mol) is added. Heating to 80° C. is thencarried out and 1-bromododecane is added dropwise under a protective gasatmosphere. The suspension is heated at reflux for a further 16 hours.After cooling to 25° C., filtration is carried out, the residue is thenwashed several times with ethanol and the combined filtrates areconcentrated to dryness by evaporation. The residue is dissolved intert-butyl methyl ether. Washing is then carried out with 1M aqueoussodium hydroxide solution (3×200 ml) and water (1×200 ml), and theorganic phase is dried over Na₂SO₄, filtered off and concentrated todryness by evaporation.

[0321] Yield: 166 g (79%)

[0322] b) 1-Nitro-2-(4-dodecyloxy-3-methoxyphenyl)ethene

[0323] 4-Dodecyloxy-3-methoxybenzaldehyde (166 g; 0.519 mol) is heatedfor 2 hours at 100° C. with ammonium acetate (20 g; 0.388 mol) andnitromethane (49 ml; 0.914 mol). The resulting melt is then addeddropwise with vigorous stirring to methanol, yellow crystalsprecipitating. After filtration, the residue is washed several timeswith methanol and then dried.

[0324] Yield: 122.3 g (51% based on vanillin)

[0325] NMR (δ in ppm; CDCl₃):

[0326]¹H-NMR: 8.0 (1H, d, 13.5 Hz); 7.55 (1H, d, 13.5 Hz); 7.18 (1H, d,8.5 Hz); 7.05 (1H, s); 6.92 (1H, d, 8.5 Hz); 4.10 (2H, t, 7.8 Hz); 3.95(3H, s); 1.93 (2H, m); 1.51 (2H, m); 1.40 (16H, m); 0.92 (3H, t, 7.8 Hz)

[0327]¹³C-NMR: 153.0; 150.2; 139.9; 135.4; 125.1; 122.9; 112.8; 111.1;69.6; 56.5; 32.3; 30.1; 30.03; 29.98; 29.93; 29.75; 29.34; 26.3; 23.10;14.52

[0328] c) 1-Amino-2-(4-dodecyloxy-3-methoxyphenyl)ethane

[0329] 1-Nitro-2-(4-dodecyloxy-3-methoxyphenyl)ethene (5.7 g; 16 mmol)is suspended in THF ((100 ml) under a protective gas atmosphere. LAHsolution (1M in THF; 56 ml, 56 mmol) is then slowly added dropwise. Whenthe addition is complete, heating at reflux is carried out for 2 hoursand stirring is then carried out for a further 16 hours at 25° C. ExcessLAH is then decomposed with water (8 ml), 15% sodium hydroxide solution(8 ml) and again with water (24 ml). The suspension is stirred for afurther 30 minutes at 25° C. and then filtration is carried out. Thefiltrate is concentrated to dryness by evaporation, and the brownresidue is taken up in 10% aqueous hydrochloric acid (12 ml) and washedwith tert-butyl methyl ether (3×10 ml). The aqueous phase is renderedalkaline with 15% sodium hydroxide solution (6 ml) and extracted withtert-butyl methyl ether (3×10 ml). The organic extracts are combined,washed with water and saturated sodium chloride solution, and dried overK₂CO₃. Filtration is followed by concentration to dryness byevaporation, and freeze-drying is carried out from tert-butylalcohol/water (4:1) with the addition of hydrochloric acid.

[0330] Yield: 1.85 g (12%)

[0331] NMR (δ in ppm; DMSO-D6):

[0332]¹H-NMR: 8.1 (2.5 H, broad, NH); 6.88 (1H, d); 6.88 (1H, s); 6.74(1H, d); 3.93 (2H, t); 3.78 (3H, s); 3.02 (2H, m); 2.82 (2H, m); 1.80(2H, m); 1.43 (2H; m); 1.30 (16H, m); 0.88 (3H, t)

[0333]¹³C-NMR (CDCl₃): 148.4; 146.6; 127.5; 119.7; 112.1; 111.4; 76.07;67.97; 54.95; 40.23; 32.14; 30.77; 28.49; 28.31; 28.20; 28.08; 24.84;21.54; 12.96

[0334] MS: [M+H]⁺ m/z=336

EXAMPLE 7

[0335] a) Dodecyloxybenzene

[0336] Phenol (47 g; 0.5 mol) is dissolved in DMF (300 ml), and K₂CO₃(82.93 g; 0.6 mol) is added. 1-Bromododecane (124.6 g; 0.5 mol) is thenadded dropwise to the solution at 70° C. After a further 15 hours at 80°C., cooling to 25° C. is carried out, followed by dilution with water(500 ml) and extraction with tert-butyl methyl ether (2×250 ml). Thecombined organic extracts are washed with water (2×250 ml) and driedover Na₂SO₄. After filtration, concentration to dryness by evaporationis carried out. p0 Yield: 114 g (86.9%)

[0337] b) 4-Dodecyloxybenzaldehyde

[0338] Dodecyloxybenzene (2.48 g; 9.45 mmol) is dissolved inN-methylformanilide (195.17 g; 9.45 mmol). POCl₃ (1.45 g; 159.33 g; 9.45mmol) is added dropwise with ice-cooling. Stirring is carried out for 1hour at 25° C., and then for 3 hours at 60° C. Pouring onto ice is thencarried out and the pH is adjusted to 6 using sodium hydroxide solution.Extraction is then carried out with tert-butyl methyl ether (2×50 ml),and the combined organic phases are washed with aqueous NaHCO₃ solutionand dried over Na₂SO₄. After filtration, concentration to dryness byevaporation is carried out.

[0339] Yield: 2.72 g (98.9%)

[0340] NMR (δ in ppm; DMSO-D6):

[0341]¹H-NMR: 9.82 (1H, s); 7.78 (2H, d, 8.5 Hz); 6.92 (2H, d; 8.5 Hz);3.97 (2H, t); 1.71 (2H, m); 1.38 (2H, m); 1.20 (16H, m); 0.84 (3H, t)

[0342]¹³C-NMR: 189.8; 163.1; 131.3; 129.3; 114.0; 67.39; 31.00; 28.81;28.77; 28.73; 28.52; 28.48; 26.10; 21.73; 13.20

[0343] c) 1-Nitro-2-(4-dodecyloxyphenyl)ethene

[0344] 4-Dodecyloxybenzaldehyde (7.91 g; 27.25 mmol), ammonium acetate(1.57 g; 20.4 mmol) and nitromethane (2.57 ml; 48 mmol) are mixedtogether and the mixture is heated for 1.5 hours at 105° C. Cooling to25° C. and extraction with tert-butyl methyl ether (50 ml) are thencarried out, and the organic phase is dried over Na₂SO₄. Afterfiltration, concentration to dryness by evaporation is carried out andthe residue is suspended in methanol (80 ml). Filtration is then carriedout, and the pale yellow crystals are washed with methanol and dried invacuo.

[0345] Yield: 4.75 g (52.3%)

[0346] NMR (δ in ppm; DMSO-D6):

[0347]¹H-NMR: 8.10 (2H, 2d, 13 Hz); 7.81 (2H, d; 8.5 Hz); 6.99 (2H, d;8.5 Hz); 4.02 (2H, t); 1.72 (2H, dd); 1.38 (2H, m); 1.28 (16H, m); 0.85(3h, t)

[0348]¹³C-NMR: 165.1; 142.5; 138.8; 135.1; 128.5; 125.6; 118.3; 70.9;34.39; 32.10; 32.06; 31.80; 31.57; 28.49; 25.19; 17.04

[0349] d) 1-Amino-2-(4-dodecyloxyphenyl)ethane

[0350] Analogous to Example 6c) starting material:1-nitro-2-(4-dodecyloxyphenyl)ethene (3.33 g; 10 mmol)

[0351] Yield: 1.20 g (39.6%)

[0352] NMR (δ in ppm; DMSO-D6):

[0353]¹H-NMR: 7.84 (3H, broad, NH₃); 7.17 (2H, d, 8.5 Hz); 6.87 (2H, d;8.5 Hz); 3.90 (2H, t); 3.00 (2H, m); 2.78 (2H, t); 1.69 (2H, m); 1.45(2H, m); 1.30 (16H, m); 0.87 (3H, t)

[0354] MS. [M+H]⁺: m/z=306

EXAMPLE 8

[0355] a) 1,2-Dihexyloxybenzene

[0356] Pyrocatechol (55.1 g; 0.5 mol) is dissolved in DMF (400 ml), andK₂CO₃ (207.3 g) is added. The mixture is heated to 70° C. 1-Bromohexane(198 g; 1.2 mol) is then added dropwise, and heating is carried out for15 hours at 80° C. Further DMF (400 ml) and water (1 litre) aresubsequently added. Extraction is then carried out with tert-butylmethyl ether (2×500 ml), and the organic phase is washed with water(3×100 ml) and dried over Na₂SO₄. After filtration, concentration todryness by evaporation is carried out.

[0357] Yield: 137.7 g (98.9%)

[0358] NMR (δ in ppm; DMSO-D6):

[0359]¹H-NMR: 6.95 (2H, m); 6.85 (2H, m); 3.92 (4H, t, 7.5 Hz); 1.70(4H, m); 1.47 (4H, m); 1.35 (8H, m); 0.88 (6H)

[0360]¹³C-NMR: 149.6; 121.8; 115.0; 69.27; 33.40; 32.08; 26.10; 22.97;14.70

[0361] b) 3,4-Dihexyloxybenzaldehyde

[0362] 1,2-Dihexyloxybenzene (11.14 g; 40 mmol) and N-methylformanilide(5.41 g; 40 mmol) are cooled to 0° C., and phosphorus oxychloride (6.13g; 40 mmol) is added. Heating is then carried out for 1 hour at 25° C.,followed by stirring for 4 hours at 60° C. The reaction mixture ispoured onto ice and then adjusted to pH 6. Extraction is carried outwith tert-butyl methyl ether (2×200 ml), and washing is carried out withNaHCO₃ (2×100 ml). The organic phase is dried over Na₂SO₄, filtered andconcentrated to dryness by evaporation.

[0363] Yield: 10.8 g (87.8%)

[0364] NMR (δ in ppm; DMSO-D6):

[0365]¹H-NMR: 9.87 (1H, s); 7.55 (1H, d, 8.5 Hz); 7.40 (1H, s); 7.12(1H, d, 8.5 Hz); 4.17 (2H, t; 7.5 Hz); 4.08 (2H, t; 7.5 Hz); 1.85 (4H,m), 1.48 (4H, m); 1.33 (8H, m); 0.90 (6H, t, 7.5 Hz)

[0366]¹³C-NMR: 192.1; 154.9; 149.6; 130.4; 126.7; 126.3; 113.2; 112.1;69.27; 69.18; 31.83; 31.81; 29.46; 29.35; 26.05; 26.01; 22.95; 14.68

[0367] c) 1-Nitro-2-(3,4-dihexyloxyphenyl)ethene

[0368] 3,4-Dihexyloxybenzaldehyde (122.6 g; 0.4 mmol) is heated to 100°C. with ammonium acetate (23.12 g; 0.3 mol) and nitromethane (42.7 g;0.7 mol). Working-up is analogous to Example 6b).

[0369] Yield: 119.4 9 (85.4%)

[0370] NMR (δ in ppm; DMSO-D6):

[0371]¹H-NMR: 8.25 (1H, d; 13.5 Hz); 8.05 (1H, d; 13.5 Hz); 7.50 (1H,s); 7.39 (1H, d, 8.5 Hz); 7.03 (1H, d, 8.5 Hz); 4.06 (4H, 2t); 1.76 (4H,m); 1.48 (4H, m); 1.35 (8H, m); 0.92 (6H, 2t)

[0372]¹³C-NMR: 154.9; 151.3; 142.5; 138.4; 128.3; 125.4; 115.5; 71.07;70.88; 33.54; 31.21; 31.11; 27.80; 27.74; 24.70; 24.67; 16.45

[0373] d) 1-Amino-2-(3,4-dihexyloxyphenyl)ethane

[0374] 1-Nitro-2-(3,4-dihexyloxyphenyl)ethene (30 g; 85.8 mmol) isdissolved in ethanol with the addition of hydrochloric acid andtransferred to a hydrogenation autoclave charged with Pd/C. Cooling isthen carried out, and hydrogen is introduced until no further reactiontakes place. Filtration is then carried out over a silica gel column,followed by concentration to dryness by evaporation.

[0375] Yield: 29.08 g (94.7%)

[0376] NMR (δ in ppm; DMSO-D6):

[0377]¹H-NMR: 8.10 (3H, b; NH₃); 6.87 (2H, d; 8.5 Hz); 6.83 (1H, s);6.75 (2H, d); 3.93 (4H, 2t); 2.76-3.18 (4H, m); 1.70 (4H, m); 1.42 (4H,m); 1.28 (8H, m); 0.85 (6H, 2t)

[0378] MS: [M+H]⁺: m/z=322

EXAMPLE 9 Determination of the Minimum Inhibitory Concentration (MICValue) in Microtitre Plates Nutrient Medium

[0379] Casein/soybean flour peptone bouillon for the preparation ofpre-cultures of the test bacteria and yeast.

[0380] Mycological slant agar for the pre-culture of moulds

Examples of Test Organisms

[0381] Bacteria: Staphylococcus hominis DMS 20328 (= SH) Staphylococcusaureus ATCC 9144 Staphylococcus epidermidis ATCC 12228 Escherichia coliNCTC 8196 (= EC) Pseudomonas aeruginosa CIP A-22 (= PA) Corynebacteriumxerosis ATCC 373 Propionibacterium acnes ATCC11829 Actinomyces viscosumDSM 43329 Streptococcus sobrinus DSM 20742 Streptococcus mutans ATCC25175 Enterococcus hirae ATCC 10541 Porphyromonas gingivalis DSM 20709Selenomonas artemidis ATCC 43528 Yeasts: Candida albicans ATCC 10231 (=CA) Malassezia furfur DSM 6171 Mould: Aspergillus niger ATCC 6275 (= AN)Trichophyton mentagrophytes ATCC 9533 Trichophyton rubrum DSM 4167Epidermophyton floccosum DSM 10709

Procedure

[0382] The test substances are pre-dissolved in dimethyl sulfoxide(DMSO) and tested in a dilution series of 1:2.

[0383] Bacteria and yeast are cultured overnight in CASO bouillon, themould is cultured overnight on mycological slant agar, and washed offwith 10 ml of 0.85% sodium chloride solution (+0.1% TritonX-100).

[0384] All the test organisms are adjusted to an organism count of1−5×10⁶ CFU/ml using 0.85% sodium chloride solution.

[0385] The test substances are pre-pipetted into microtitre plates in anamount of 8 μl per well.

[0386] Pre-diluted organism suspensions are diluted 1:100 in CASObouillon (bacteria and yeast) or Sabouraud 2% glucose bouillon (mould)and are added in an amount of 192 μl per well to the test substances.

[0387] The test batches are incubated for 48 hours at 37° C. (bacteriaand yeast) or for 5 days at 28° C. (mould).

[0388] After incubation, the growth is evaluated by reference to theturbidity of the test batches (optical density) at 620 nm in amicroplate reader.

[0389] The minimum inhibitory concentration (MIC value) is theconcentration of substance at which (compared with the growth of thecontrol) an appreciable inhibition of growth (≦20% growth) of the testorganisms is ascertained.

[0390] One microtitre plate is used for each test organism and substanceconcentration. All the substances are tested in duplicate.

[0391] The results are compiled in Table 2: TABLE 2a MIC values in ppmfor various microorganisms*) General structural formula

MIC MIC MIC MIC MIC Compound [ppm] [ppm] [ppm] [ppm] [ppm] of formula R₁= R₁ SH EC PA CA AN  4

30 60 >120 60 7.5  5

7.5 15 >120 15 7.5  6

7.5 15 120 7.5 120  7

3.75 7.5 120 3.75 >120  8

7.5 7.5 >120 15 >120  9

3.75 3.75 >120 7.5 >120 10

3.75 7.5 >120 3.75 >120 11

120 >120 >120 >120 >120 12

60 120 >120 >120 30 13

120 120 >120 >120 >120 14

7.5 30 120 30 >120 15

30 30 120 30 >120 16

7.5 7.5 120 7.5 >120 17

12 24 >120 60 >120 18

1.9 >60 >120 60 >120 19

28 28 >120 60 >120 20

3.75 >120 >120 >120 >120 21

>120 >120 >120 >120 120 22

>120 >120 >120 >120 >120 23

>120 >120 >120 >120 15 24

>120 >120 >120 >120 15 25

>120 >120 >120 >120 15 26

>120 >120 >120 >120 >120 27

>120 >120 >120 >120 >120 28

>120 >120 >120 >120 >120 29

>120 >120 >120 >120 >120 30

120 120 >120 120 >120 31

>120 >120 >120 >120 >120 32

>120 >120 >120 >120 >120 33

30 15 120 30 >120 34

15 15 120 15 >120 35

60 60 >120 60 >120 36

3.75 3.75 >120 3.75 >120 37

3.75 30 >120 30 >120 38

7.5 >120 >120 >120 >120 39

60 >120 >120 >120 >120 40

>120 >120 >120 >120 >120 41

120 120 >120 120 >120 42

>120 >120 >120 >120 >120 43

>120 >120 >120 >120 >120 44

60 60 >120 60 >120 45

15 3.75 >120 7.5 >120 46

>100 >100 >120 >120 >120 47

60 120 >120 >120 >120 48

>52 >52 >120 >120 120 49

>120 >120 >120 >120 >120 50

>120 >120 >120 >120 >120 51

>120 >120 >120 >120 >120 52

>120 120 >120 >120 120 53

3,75 >120 >120 15 30 54

7.5 7.5 >120 15 60

[0392] TABLE 2b MIC values in ppm for various microorganisms*) Generalstructural formula

Compound MIC MIC MIC MIC MIC of formula R₁ = R₂ = R₃ [ppm]SH [ppm]EC[ppm]PA [ppm]CA [ppm]AN 55

15 30 >120 >120 15 56

7.5 120 >120 30 7.5 57

7.5 >120 >120 30 >120 58

7.5 >120 >120 15 15 59

60 >120 >120 120 >120 60

30 >120 >120 120 >120 61

60 >120 >120 120 >120 62

>120 >120 >120 60 120 63

120 >120 >120 60 >120 64

>120 >120 >120 60 15 65

15 >120 >120 60 >120 66

15 15 >120 120 >120 67

3.75 7.5 >120 7.5 >120 68

3.75 3.75 >120 3.75 >120 69

>120 >120 >120 >120 >120 70

7.5 7.5 >120 15 >120 71

>120 >120 >120 >120 >120 72

>120 >120 >120 >120 >120 73

>120 >120 >120 >120 >120 74

>120 >120 >120 >120 >120 75

60 >120 >120 >120 >120 76

21>120 >120 >120 >120 >120 77

120 >120 >120 >120 >120 78

>120 >120 >120 >120 >120 79

>120 >120 >120 >120 120 80

120 120 >120 >120 120 81

15 7,5 120 30 >120 82

>120 >120 >120 >120 >120 83

>120 30 >120 120 >120 84

3.75 7.5 >120 15 15 85

30 15 >120 7.5 15 86

7.5 15 >120 60 30 87

15 >120 >120 >120 15 88

>120 >120 >120 >120 >120 89

>120 >120 >120 >120 >120 90

>120 >120 >120 >120 >120 91

>120 >120 >120 >120 >120 92

15 15 >120 60 120 93

>120 >120 >120 >120 >120 94

60 60 >120 120 >120 95

15 7.5 120 30 120 96

7.5 >120 >120 >120 60 97

>120 >120 >120 >120 >120 98

30 30 >120 >120 >120 99

60 60 >120 >120 >120

[0393] TABLE 2c MIC values in ppm for various microorganisms Compoundtested (100) (101) (102) MIC MIC MIC Microorganism [ppm] [ppm] [ppm]Staphylococcus aureus ATCC 9144 25 13 13 Staphylococcus epidermidis ATCC12228 13 13  6 Staphylococcus hominis DSM 20328  2  8  4 Corynebacteriumxerosis ATCC 373  6  6  6 Propionibacterium acnes ATCC11829 50 — 13Actinomyces viscosum DSM 43329 25 — 13 Streptococcus sobrinus DSM 20742 6 13  6 Enterococcus hirae ATCC 10541 25 50 13 Streptococcus mutansATCC 25175  6  6  3 Escherichia coli NCTC 8196 — —  4 Pseudomonasaeruginosa CIP A 22 — — — Porphyromonas gingivalis DSM 20709 25 25  2Selenomonas artemidis ATCC 43528 — — 25 Aspergillus niger ATCC 6275  2 1 — Trichophyton mentagrophytes ATCC 9533 — — 25 Trichophyton rubrumDSM 4167 — 13 25 Epidermophyton floccosum DSM 10709  3  3  6 Malasseziafurfur DSM 6171 — — — Candida albicans ATC 10231  2 50  4

What is claimed is:
 1. The use of a compound of formula

wherein R₁, R₂ and R₃are each independently of the others hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted or C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-, carboxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- ordi-C₁-C₂₀alkylamino- or nitro-substituted phenyl, phenyl-C₁-C₅alkyl,biphenyl, biphenyl-C₁-C₅alkyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl; R₄, R₅, R₆ and R₇ are eachindependently of the others hydrogen; C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl;C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl; C₃-C₂₀alkynyl; or C₄-C₁₂cycloalkynyl;and m and n are each independently of the other 0 or 1; for theantimicrobial treatment of surfaces.
 2. Use according to claim 1, whichrelates to a compound of formula (1) wherein R₄, R₅, R₆ and R₇ arehydrogen.
 3. Use according to claim 1 or 2, which relates to a compoundwherein n is 0; and m is
 1. 4. Use according to any one of claims 1 to3, which relates to a compound of formula

wherein R₂ and R₃ are each independently of the other phenyl-C₁-C₅alkylunsubstituted or substituted by C₁-C₅alkyl, C₂-C₆alkenyl,C₃-C₁₂cycloalkyl, C₁-C₅alkoxy, C₃-C₁₂cycloalkoxy, halogen, oxo, carboxy,carboxy-C₁-C₇alkyl ester, carboxy-C₃-C₁₂cycloalkyl ester, cyano,trifluoromethyl, pentafluoroethyl, amino, N,N-mono- ordi-C₁-C₂₀alkylamino or by nitro.
 5. Use according to claim 4, wherein R₂and R₃ are C₁-C₅alkyl or C₄-C₁₂cycloalkyl.
 6. Use according to claim 4,wherein R₂and R₃ are C₂-C₆alkenyl.
 7. Use according to claim 1, whichrelates to a compound of formula

wherein R₁, R₂ and R₃ are each independently of the othersphenylcarbonyl-C₁-C₅alkyl unsubstituted or substituted by C₁-C₅alkyl,C₂-C₆alkenyl, C₄-C₁₂cycloalkyl, C₁-C₅alkoxy, C₃-C₁₂cycloalkoxy, halogen,oxo, carboxy, carboxy-C₁-C₇alkyl ester, carboxy-C₃-C₁₂cycloalkyl ester,cyano, trifluoromethyl, pentafluoroethyl, amino, N,N-mono- ordi-C₁-C₂₀alkylamino or by nitro.
 8. Use according to claim 7, whereinR₁, R₂ and R₃ are each independently of the others C₁-C₅alkyl orC₄-C₁₂cycloalkyl.
 9. Use according to claim 7, wherein R₁, R₂ and R₃ areeach independently of the others C₂-C₆alkenyl.
 10. A process for thepreparation of a compound of formula (1) according to claim 1, whereinthe compound is prepared in solid-phase synthesis, using a trityl resin(TCP), according to the following scheme:

wherein R is C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl;C₄-C₁₂cycloalkenyl; C₃-C₂₀alkynyl; C₄-C₁₂-cycloalkynyl; or unsubstitutedor C₁-C₅alkyl-, C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-,halo-, oxo-, carboxy-, carboxy-C₁-C₇alkyl ester-,carboxy-C₃-C₁₂cycloalkyl ester-, cyano-, trifluoromethyl-,pentafluoroethyl-, amino-, N,N-mono- or di-C₁-C₂alkylamino- ornitro-substituted phenyl, phenyl-C₁-C₅alkyl, biphenyl,biphenyl-C₁-C₅alkyl, naphthyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl,isoquinolinylalkyl,, pyrrolyl, furanyl, thiophenyl, pyrazolyl,imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl,1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl,pyrimidinyl, pyridazinyl, quinolinyl or isoquinolinyl; X is F, Cl, Br, Ior hydroxy; and n is from 1 to
 3. 11. A process for the preparation of acompound of formula

by alkylation of an n-hydroxybenzoic acid alkyl ester (step 1),hydrogenation with LiAIH₄ to form the alkylated benzyl alcohol (step 2),reaction with thionyl chloride to form the corresponding alkyl halidecompound (step 3), reaction with KCN to form the corresponding nitrilecompound (step 4) and subsequent reduction with LiAIH₄ to form the aminocompound of formula (103) (step 5) in liquid-phase synthesis accordingto the following scheme:

wherein R is C₁-C₂₀alkyl; C₃-C₇cycloalkyl; or phenyl-C₁-C₅alkylunsubstituted or substituted by C₁-C₅alkyl, C₃-C₇cycloalkyl,C₁-C₅alkoxy, C₃-C₇cycloalkoxy, halogen, oxo, carboxy, carboxy-C₁-C₇alkylester, carboxy-C₃-C₇cycloalkyl ester, cyano, trifluoromethyl,pentafluoroethyl, amino, N,N-mono- or di-C₁-C₂₀alkylamino or by nitro;Hal is a halogen atom; and n is from 1 to
 3. 12. A process for thepreparation of a compound of formula (1) according to claim 1, whereinthe deprotonated phenol or mono- or di-hydroxyphenol is alkylated, andthen reacted with phosphorus oxychloride and an N,N-dialkylated amideand the benzaldehyde is isolated after hydrolysis (reaction step (1a)),or the phenol or mono- or di-hydroxyphenol is reacted with phosphorusoxychloride and an N,N-dialkylated amide and alkylated (reaction step(1b)), the aldehyde is heated with a mixture of ammonium acetate and anitroalkane in a suitable solvent, and the nitrostyrene is hydrogenatedcatalytically to form phenylethylamine (reaction step (2)), according tothe following reaction scheme:

wherein R₁ and R₂ are each independently of the other hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀-alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted or C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-, carboxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- ordi-C₁-C₂₀alkylamino- or nitro-substituted phenyl, phenyl-C₁-C₅alkyl,biphenyl, biphenyl-C₁-C₅alkyl, naphthyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl; X is Cl, Br or I; and m isfrom 0 to
 2. 13. Use of a compound of formula (1) for the antimicrobialtreatment, deodorisation and disinfection of the skin, mucosa and hair.14. Use according to claim 13, wherein the compound of formula (1) isused for disinfection and deodorisation.
 15. Use of a compound offormula (1) for the treatment of textile fibre materials.
 16. Useaccording to claim 15, wherein the compound of formula (1) is used forpreservation.
 17. Use of a compound of formula (1) in washing andcleaning formulations.
 18. Use of a compound of formula (1) in impartingantimicrobial properties to and preserving plastics, paper, nonwovens,wood or leather.
 19. Use of a compound of formula (1) in impartingantimicrobial properties to and preserving technical products,especially print thickeners of starch or of cellulose derivatives,surface-coatings and paints.
 20. Use of a compound of formula (1) as abiocide in technical processes, especially in paper treatment.
 21. Apersonal care preparation comprising from 0.01 to 15% by weight, basedon the total weight of the composition, of a compound of formula (1),and cosmetically tolerable adjuvants.
 22. An oral composition comprisingfrom 0.01 to 15% by weight, based on the total weight of thecomposition, of a compound of formula (1), and orally tolerableadjuvants.
 23. A compound of formula

wherein R′₁, R′₂ and R′₃ are each independently of the others hydrogen;C₁-C₂₀alkyl; C₃-C₁₂cycloalkyl; C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl;C₃-C₂₀alkynyl; C₄-C₁₂cycloalkynyl; or unsubstituted or C₁-C₅alkyl-,C₃-C₁₂cycloalkyl-, C₁-C₅alkoxy-, C₃-C₁₂cycloalkoxy-, halo-, oxo-,carboxy-,carboxy-C₁-C₇alkyl ester-, carboxy-C₃-C₁₂cycloalkyl ester-,cyano-, trifluoromethyl-, pentafluoroethyl-, amino-, N,N-mono- ordi-C₁-C₂₀alkylamino- or nitro-substituted phenyl, phenyl-C₁-C₅alkyl,biphenyl, biphenyl-C₁-C₅alkyl, naphthyl, naphthyl-C₁-C₅alkyl,phenylcarbonyl-C₁-C₅alkyl, naphthylcarbonyl-C₁-C₅alkyl, pyrrolylalkyl,furanylalkyl, thiophenylalkyl, pyrazolylalkyl, imidazolylalkyl,oxazolylalkyl, thiazolylalkyl, isoxazolylalkyl, isothiazolylalkyl,1,2,3-triazolylalkyl, 1,2,4-triazolylalkyl, 1,2,3-oxadiazolylalkyl,1,3,4-oxadiazolylalkyl, 1,2,3-thiadiazolylalkyl,1,3,4-thiadiazolylalkyl, indolylalkyl, pyridylalkyl, pyridazinylalkyl,pyrimidinylalkyl, pyridazinylalkyl, quinolinylalkyl, isoquinolinylalkyl,pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl,thiazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl,1,3,4-thiadiazolyl, indolyl, pyridyl, pyridazinyl, pyrimidinyl,pyridazinyl, quinolinyl or isoquinolinyl; R′₄, R′₅, R′₆ and R′₇ are eachindependently of the others hydrogen; C₁-C₂₀alkyl; C₃-C₁₂-cycloalkyl;C₂-C₂₀alkenyl; C₄-C₁₂cycloalkenyl; C₃-C₂₀alkynyl; or C₄-C₁₂cycloalkynyl;and m′ and n′ are each independently of the other 0 or 1, with theexclusion of compounds of formula (1′) wherein n′ is1; and m′ is 0; andsimultaneously R′₁, and R′₂ are C₁-C₅alkyl, C₂-C₅alkenyl; benzyl; or aradical of formula

R′₈ is C₁-C₄alkyl; R′₄, R′₅, R′₆ and R′₇ are hydrogen, and of compoundsof formula (1′) wherein n′ and m′ are 1; R′₁, R′₂ and R′₃ are benzyl;and R′₄, R′₅, R′₆ and R′₇ are hydrogen.